1. Field of the Invention
The present invention relates to a method of treating retroviral infections in mammals via the use of camptothecin (CPT) and similar compounds which act as inhibitors of retroviral topoisomerase I, blocking the initiation of retroviral infection and replication in target cells and reducing and eliminating viral production by cells infected with such viruses, thereby reducing or eliminating the viral infection and its consequences in infected individuals. As a consequence of this mechanism of action, these compounds should find wide utility in both human and veterinary medicine.
2. Description of Related Art
Weis et al. ((1981) Virology 114: 563-66) have described the detection of DNA topoisomerase activity associated with the Prague C strain of Rous Sarcoma Virus. The enzyme activity was partially purified from viral extracts using standard biochemical techniques, and compared to the chicken cellular topoisomerase. Both showed identical behavior in response to different concentrations of magnesium, and both were indistinguishable with respect to size (40,000-60,000 daltons) upon glycerol gradient centrifugation. The authors concluded that the "viral" enzyme most probably represented non-specific incorporation of the cellular topoisomerase into the viral particle. The exact nature of the topoisomerase was not further analyzed, and the authors indicated that its role in the retroviral life cycle was indeterminant. The conclusion that the viral enzyme was a cellular contaminant, however, would imply a non-essential role.
Snapka ((1986) Mol. Cell. Biol. 6: 4221-27) reported that camptothecin selectively interferes with Simian Virus 40 DNA replication.
The use of camptothecin and similarly acting compounds for treating retrovirus infections has yet to be reported.